rs4103

Positions:

chr13-110445879-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001846.4(COL4A2):c.1008C>T(p.Pro336=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 1,613,490 control chromosomes in the GnomAD database, including 227,167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 18597 hom., cov: 32)

Exomes 𝑓: 0.53 ( 208570 hom. )

Consequence

COL4A2
NM_001846.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.347

Variant links:

Genes affected

COL4A2 (HGNC:2203): (collagen type IV alpha 2 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. The C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. [provided by RefSeq, Jul 2008]

COL4A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 13-110445879-C-T is Benign according to our data. Variant chr13-110445879-C-T is described in ClinVar as [Benign]. Clinvar id is 311117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110445879-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.347 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4 linkuse as main transcript	c.1008C>T	p.Pro336=	synonymous_variant	17/48	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
COL4A2	ENST00000360467.7 linkuse as main transcript	c.1008C>T	p.Pro336=	synonymous_variant	17/48	5	NM_001846.4	ENSP00000353654	P1
COL4A2	ENST00000650540.1 linkuse as main transcript	c.1008C>T	p.Pro336=	synonymous_variant	17/18			ENSP00000497878
COL4A2	ENST00000617564.2 linkuse as main transcript	c.267C>T	p.Pro89=	synonymous_variant	5/10			ENSP00000481492

Frequencies

GnomAD3 genomes

AF:

0.492

AC:

74703

AN:

151908

Hom.:

18579

Cov.:

show subpopulations

Gnomad AFR

AF:

0.401

Gnomad AMI

AF:

0.642

Gnomad AMR

AF:

0.482

Gnomad ASJ

AF:

0.450

Gnomad EAS

AF:

0.535

Gnomad SAS

AF:

0.536

Gnomad FIN

AF:

0.495

Gnomad MID

AF:

0.414

Gnomad NFE

AF:

0.543

Gnomad OTH

AF:

0.484

GnomAD3 exomes

AF:

0.511

AC:

127547

AN:

249516

Hom.:

33022

AF XY:

0.514

AC XY:

69578

AN XY:

135368

show subpopulations

Gnomad AFR exome

AF:

0.396

Gnomad AMR exome

AF:

0.495

Gnomad ASJ exome

AF:

0.426

Gnomad EAS exome

AF:

0.525

Gnomad SAS exome

AF:

0.521

Gnomad FIN exome

AF:

0.498

Gnomad NFE exome

AF:

0.538

Gnomad OTH exome

AF:

0.496

GnomAD4 exome

AF:

0.533

AC:

778336

AN:

1461464

Hom.:

208570

Cov.:

AF XY:

0.533

AC XY:

387803

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.397

Gnomad4 AMR exome

AF:

0.493

Gnomad4 ASJ exome

AF:

0.429

Gnomad4 EAS exome

AF:

0.567

Gnomad4 SAS exome

AF:

0.524

Gnomad4 FIN exome

AF:

0.498

Gnomad4 NFE exome

AF:

0.543

Gnomad4 OTH exome

AF:

0.513

GnomAD4 genome

AF:

0.492

AC:

74747

AN:

152026

Hom.:

18597

Cov.:

AF XY:

0.491

AC XY:

36457

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.401

Gnomad4 AMR

AF:

0.482

Gnomad4 ASJ

AF:

0.450

Gnomad4 EAS

AF:

0.535

Gnomad4 SAS

AF:

0.537

Gnomad4 FIN

AF:

0.495

Gnomad4 NFE

AF:

0.543

Gnomad4 OTH

AF:

0.480

Alfa

AF:

0.517

Hom.:

26827

Bravo

AF:

0.482

Asia WGS

AF:

0.495

AC:

1723

AN:

3476

EpiCase

AF:

0.530

EpiControl

AF:

0.525

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 02, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Porencephaly 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.9

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over